1. Thrombolytic drugs
BY :DR. ISRAA OMAR

2. Fibrinolysis and thrombolysis
It is initiated concomitantly with coagulation cascade, resulting in the formation of active plasmin ,which digest fibrin .
The main drug of this group are streptokinase and tissue plasminogen activator (tPA),for example alteplase
The main use is in acute STMI ,acute stroke ,clearing cannula ,arterial thromboembolism and life threatening DVT and pulmonary embolism

3. Thrombolytic drugs – mechanism of action

4. Thrombolytic drugs – mechanism of action

5. Thrombolytic drugs – mechanism of action

6. 1. Streptokinase
Is a non –enzyme protein extracted from culture of streptococci
It form stable complex with plasminogen and gains enzymic activity ;then causes fibrinolysis
The major adverse effect is bleeding include GI Hemorrhage and stroke
Hemorrhage can be treated with traneximic acid
Hypotension and hypersensitivity may also recorded

7. 2. Alteplase and duteplase
Both are recombinant tissue plasminogen activators.
Alteplase is a single chain where as duteplase is a double chain
They preferentially plasminogen that is bound to fibrin ,they are said to be clot selective .
They dissolve formed thrombus and avoid systemic activation of plasminogen
They can cause hemorrhage but less than streptokinase
No hyper sensitivity reaction occur with them

8. Contraindications to thrombolytic therapy
Active internal bleeding
Bleeding diatheses
Pregnancy
Uncontrolled hypertension
CPR (Cardio-plumonary resuscitation)
Recent major surgery or Eye surgery
Recent hemorrhagic stroke 8- dissecting aorta aneurysm 9- Brain tumors

9. Treatment of bleeding
BY:DR ISRAA OMAR

10. Drugs for Bleeding Disorders
Coagulation Factors
Inhibitors of fibrinolysis
Vitamin K
Factor VIII
Factor IX
Desmopressin
Aminocaproic Acid
Tranexamic Acid
Aprotinin

11. 1. Antiplasmin drugs
Aminocaproic acid and tranexamic acid both are synthetic agents. They are orally active
Mechanism of action
They are lysine analogs that bind to plasminogen and plasmin, thus blocking both the conversion of plasminogen to plasmin and the binding of plasmin to target fibrin.
The drugs are potent inhibitors of fibrinolysis and can reverse states associated with excessive fibrinolysis.

12. Adverse effects
Intravascular thrombosis, a major adverse effect due to inhibition of plasminogen activator.
Myopathy with rhabdomyolysis (rare)
Rhabdomyolysis is the breakdown of muscle tissue that leads to the release of muscle fiber contents into the blood.

13. Therapeutic uses
Bleeding due to fibrinolytic therapy or surgery in hemophiliacs.
Bleeding due to other causes (surgery, radiation, intracranial aneurism, cancer chemotherapy, etc.) (benefits in these settings are limited)

14. 2. Aprotinin It stops bleeding by blocking plasmin
It can inhibit streptokinase
It is used to reduce blood loss in patients undergoing cardiopulmonary bypass surgery
Side effect include anaphylactic reaction if there is previous exposure within 12 month , renal dysfunction is also reported with the use of this drug

15. 3. Protamine sulfate Antagonizes the anticoagulant effect of heparin
It is derived from fish sperm and testes and has a high content of arginine which make it basic drug
It is positive charge neutralize the negative charge of heparin thus making a stable complex and prevent the action of heparin
Side effect include dyspnea, flushing, hypotension and bradycardia especially when injected rapidly

16. 4. Vitamin k (phytonadione)
It antagonize the action of oral anticoagulant
The action of vitamin k start after 24 hours; thus, if immediate action is required, fresh frozen plasma should be infused

17. Good luck